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01-07-2009 | Short Communication

Polyinosinic polycytidylic acid prevents efficient antigen expression after mRNA electroporation of clinical grade dendritic cells

Authors: Danita H. Schuurhuis, W. Joost Lesterhuis, Matthijs Kramer, Maaike G. M. Looman, Maaike van Hout-Kuijer, Gerty Schreibelt, A. C. Inge Boullart, Erik H. J. G. Aarntzen, Daniel Benitez-Ribas, Carl G. Figdor, Cornelis J. A. Punt, I. Jolanda M. de Vries, Gosse J. Adema

Published in: Cancer Immunology, Immunotherapy | Issue 7/2009

Abstract

Tumor-derived peptides are used frequently as antigen (Ag) source in dendritic cell (DC) therapy in cancer patients. An alternative is to load DC with tumor-associated Ag (TAA)-encoding RNA. RNA-loading obviates prior knowledge of CTL and Th epitopes in the Ag. Multiple epitopes for many HLA alleles (both MHC class I and class II) are encoded by the RNA and loading is independent of the patient’s HLA make-up. Herein, we determined the optimal conditions for mRNA-electroporation of monocyte-derived DC for clinical application in relation to different maturation cocktails. The data demonstrate that TAA carcinoembryonic antigen, gp100 and tyrosinase are expressed already 30 min after electroporation with the encoding mRNA. Moreover, gp100-specific CTL are activated by gp100 mRNA-electroporated DC. Importantly, we show here that the presence of polyinosinic–polycytidylic acid [poly(I:C)] in the maturation cocktail prevents effective protein expression of the electroporated mRNA as well as subsequent CTL recognition. This effect of poly(I:C) correlates with the induction of IFN-induced genes and innate anti-viral effector molecules in DC. Together these data show that electroporation of mature DC with TAA-encoding mRNA is attractive for use in DC vaccination protocols in cancer patients, but protein expression should be tested for each maturation cocktail.

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Title: Polyinosinic polycytidylic acid prevents efficient antigen expression after mRNA electroporation of clinical grade dendritic cells
Authors: Danita H. Schuurhuis
W. Joost Lesterhuis
Matthijs Kramer
Maaike G. M. Looman
Maaike van Hout-Kuijer
Gerty Schreibelt
A. C. Inge Boullart
Erik H. J. G. Aarntzen
Daniel Benitez-Ribas
Carl G. Figdor
Cornelis J. A. Punt
I. Jolanda M. de Vries
Gosse J. Adema
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0626-y

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